Aposense Enhancing Drug Effects

Transcription

1 Aposense Enhancing Drug Effects Miri Ben-Ami, M.D. CEO IATI Biomed June 2013 Aposense Proprietary

2 FORWARD LOOKING STATEMENTS The following slides contain forward-looking statements that include, but are not limited to, projections about our business and our future revenues, expenses and profitability. Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause the actual events, results, performance, circumstances or achievements of the Company to be materially different from those expressed or implied by such forward-looking statements due to factors that include, but are not limited to: (1) our ability to develop and bring to market new products, (2) our ability to successfully complete any necessary or required clinical studies with our products, (3) our ability to receive regulatory clearance or approval to market our products or changes in regulatory environment, (4) our success in implementing our sales, marketing and manufacturing plans, (5) the level of adoption of our products by medical practitioners, (6) the emergence of other products that may make our products obsolete, (7) protection and validity of patents and other intellectual property rights, (8) the effect of competition by other companies and technologies, and (9) our ability to obtain reimbursement for our products from government and commercial payers. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of these slides. The Company undertakes no obligation to update any forward-looking statements, to report events or to report the occurrence of unanticipated events that may lead to the actual events, results, performance, circumstances or achievements of the Company being different than as envisaged by such forward looking statements. 2

3 Content 1. From imaging to therapeutics 2. Aposense technology 3. ATT-11T for solid tumors 4. Company information 5. Conclusion

4 Aposense Update Aposense Pro-Drug Active Drug Pipeline prioritisation and focus 35% operative burn-rate reduction Strategic alliances 4 CONFIDENTIAL

5 Content 1. From imaging to therapeutics 2. Aposense technology 3. ATT-11T for solid tumors 4. Company information 5. Conclusion

6 Leveraging Drug-Membrane Interactions Extending PK Selective activation Better safety profile Higher Efficacy Active Drug Aposense Pro-Drug 6

7 Camptothecin-Based Agents; Specific Inhibitors of Topo-Isomerase I SN-38 Very potent anti-cancer agent Highly toxic Problematic pharmacokinetics Very poor solubility Cannot be used as a drug Irinotecan (CPT-11) Developed to enhance water solubility of SN-38 Pro-drug of SN fold less potent than SN-38 Activated to SN-38, predominantly in the liver and plasma IV administered drug >$1Bn annual sales prior to IP expiration (2008/9) 7

8 Clinical Unmet Needs - Camptothecin-SN-38 Treatment CONFIDENTIAL 8

9 ATT-11T: A Novel SN-38 Pro-Drug SN-38 ATT-11T CONFIDENTIAL 9

10 The cell membrane as the pharmacophore Charged (phospholipid headgroups) Polar (glycerol region) Hydrocarbon core 60A

11 Membrane Simulation 20nsec ATT-11T Irinotecan

12 Concentration, ng/ml (log scale) PK in dogs of SN-38, derived from ATT-11T vs. Irinotecan Five-fold extension of SN-38 plasma half-life Slow Clearance t 1/2 (hr) SN-38 derived from ATT-11T vs. Irinotecan X ATT-11T * Not detectable Irinotecan * * irinotecan ATT-11T Results reproduced in additional species: Mice: ATT-11T and Irinotecan derived SN-38 plasma t 1/2 were 5.7hr and 1.1hr #, respectively Rat: ATT-11T and Irinotecan derived SN-38 plasma t 1/2 were 9.5hr and 2.9hr, respectively # Kaneda et al (1990), Cancer Res. 15:1715 CONFIDENTIAL 12

13 Pro-drug, ng/g Pro-drug, ng/g Bio-Distribution Study in Tumor-Bearing Mice ATT-11T yields a higher overall exposure to the pro-drug 7,000 ATT-11T Muscle 7,000 Irinotecan Muscle 6,000 5,000 Plasma Tumor 6,000 5,000 Plasma Tumor 4,000 4,000 3,000 3,000 2,000 2,000 1,000 1, Time, hr Time, hr Study design: Melanoma (A375)-tumor-bearing mice, single equimolar doses of ATT-11T (30mg/kg) or Irinotecan (27mg/kg) Tissue AUC, ng/g*hr Tissue AUC, ng/g*hr Tumor 161,216 Tumor 17,119 Plasma 93,441 Plasma 7,815 Muscle 155,195 Muscle 23,518 CONFIDENTIAL 13

14 SN-38, ng/g Bio-Distribution Study in Tumor-Bearing Mice ATT-11T yields a higher and selective tumor exposure to SN-38 SN-38, ng/g 120 ATT-11T Muscle 120 Irinotecan Muscle 100 Plasma Tumor 100 Plasma Tumor Tumor/muscle = Tumor/muscle = Time, hr Time, hr Tissue AUC, ng/g*hr Tissue AUC, ng/g*hr Tumor Plasma *Muscle 3, x3.34 x0.25 Tumor Plasma *Muscle 1, * Low SN-38 levels were also observed in all other assessed tissues: kidney, lung, heart & bone marrow CONFIDENTIAL

15 Efficacy CONFIDENTIAL 15

16 ATT-11T vs. Irinotecan in Melanoma Model Prolonged effect post end of treatment Tumor size (mm 3 ) 4000 A375-melanoma tumor-bearing mice, IV Non-Treated (Control group) Irinotecan 225mg/kg (75X3) Tumor Free Survival ATT-11T Irinotecan 40% 0% (60 days post treatment) Tx End ATT-11T 45mg/kg (5X9) Days from tumor Inoculation * No adverse effects observed Dose regimen was based on maximal tolerable dose (MTD) of Irinotecan (qwx3) in comparison to the minimal effective dose of ATT-11T (q2dx9) CONFIDENTIAL 16

17 Tumor volume, mm3 ATT-11T vs. Irinotecan in Ovarian Cancer Model Superior efficacy at equimolar doses Ovarian carcinoma-ovcar-3, IV Tumor volume, mm Control-vehicle Control - vehicle Irinotecan 3X18mg/kg ATT-11T 3X20mg/kg CPT-11 3x18mg/kg ATT-11T 3x20mg/kg % Inhibition ATT-11T 99% Irinotecan 77% P< Day Maximal possible TGD was achieved At equimolar dose, ATT-11T exhibits superior TGI and TGD compared to Irinotecan No weight loss or other adverse effects observed Performed by Piedmont Research Center, NC 17

18 ATT-11T Demonstrates Superior Efficacy at Equimolar Doses Over Irinotecan in Small-Cell Lung Carcinoma Model H-69 H-82 Tumor volume, mm Control ATT-11T 40mg/kg CPT-11 36mg/kg Tumor volume, mm Control ATT-11T 40mg/kg CPT-11 36mg/kg End of Tx Time, days Time, days

19 Colon carcinoma model (SW620): Dose response of ATT-11T administrated i.v. once a week 800 Control 700 ATT-11T 40mg/kg ATT-11T 20mg/kg Tumor volume, mm ATT-11T 10mg/kg ATT-11T 5mg/kg CPT-11 36mg/kg 20% 44% 75% % 100% n=9-10 mice/group Time, days

20 Non-Clinical Safety CONFIDENTIAL 20

21 Preliminary toxicology data demonstrates improved safety profile of ATT-11T Dog toxicology study (at Irinotecan dog MTD) Dose was well tolerated Moderate adverse effects: No early diarrhea; no cholinergic effects Late diarrhea: transient and moderate Transient leucopenia # Meyer-Losic et al. (2008) Clin. Cancer. Res. 14:2145 CONFIDENTIAL 21

22 ATT-11T development - next milestones: FDA Pre-IND, formal tox end 2013 Estimated entry into clinical trials PhI mid 2014 ATT-11T: Potential Clinical Indications Metastatic Colorectal Carcinoma 1 st Line therapy in combination with 5-FU/LV (FOLFIRI) 2 nd Line as mono-therapy (following 5-FU failure) Small Cell Lung Carcinoma Ovarian carcinoma Esophagogastric carcinoma Pancreatic carcinoma The Company s assessments and estimations regarding the above mentioned time table for the ATT-11T development next milestones depend, among other factors, on successful results from pre-clinical experiments and regulatory approvals, and other risk factors which apply to the Company s activity, as described on Company s annual reports. CONFIDENTIAL 22

23 ATT-11T: Summary Innovation Feasibility Market Novel pro-drug approach Unique mechanism of action Objectives: Inactive pro-drug depot Selective activation at the tumor target tissue Extended PK Enlargement therapeutic window NCE & new IP Lead compound in advanced preclinical assessment Superior anti-tumor activity Extended t 1/2 demonstrated in rodent and dog Bio-distribution studies support inactive depot formation and selective activation at the tumor target tissue Preliminary toxicology study indicates favorable safety profile CMC support formal toxicology studies Large market opportunity ($1-1.7Bn) Strong, clear unmet need Irinotecan is a potent cytotoxic drug - but limited: Short half life High toxicity Indicated on in CRC

24 Content 1. From Imaging to Therapeutics 2. Aposense technology 3. ATT-11T for solid tumors 4. Company information 5. Conclusion

25 Board & Management Board of Directors Alon Dumanis, PhD, Chairman CEO of Docor, of the Van Leer Foundation Ret. General, Israeli Air Force Prof. Ilan Ziv, MD, CSO Neurologist, Aposense Founder Jacob Gottenstein Chairman of Israeli Petrochemical Industries Aposense Co-Founder Morry Blumenfeld, PhD Partner, Ziegler-MediTech Partners Formerly Chief Scientist, GE Healthcare Amos Bar-Shalev President, Technorov Holdings Jospeh Dobrovsky, PhD Former, Head of Drug Procurement, Clalit HMO Chaim Hurvitz Founder & CEO, CH Health Member of BOD, TEVA Pharmaceuticals Shay Brill, MD Director General, Beit Rivka Geriatric Center Management Miri Ben-Ami, MD Chief Executive Officer Former Head Neuro/CNS Therapeutic Area, Innovative R&D, TEVA Pharmaceuticals Eli Frydman, PhD, MBA Chief Operations Officer Former Senior Business Development Manager, GE Healthcare Prof. Ilan Ziv, MD Chief Scientific Officer Neurologist, Aposense Founder Dovi Farkash, CPA, Adv. Chief Financial Officer Former VP Finance, M-Systems Menashe Levi, PhD VP Research & Development Former VP R&D Colbar, VP R&D and Co- Founder Gamida-Cell, CTO Rostam Shirith Kasher, Adv. Head of Corporate & Structured Finance, BCRE

26 Content 1. From imaging to therapeutics 2. Aposense technology 3. ATT-11T for solid tumors 4. Company information 5. Conclusion

27 Aposense Pipeline Selective Activation in Target Extending therapeutic window Extended PK Oral Administration Oncology NEW Conjugated Molecules Neurology

28 "Medicine, the only profession that labors incessantly to destroy the reason for its existence." James Bryce CONFIDENTIAL 28